Hydrogenase Enzymes and Their Synthetic Models: The Role of Metal Hydrides

Abstract

Hydrogenase enzymes efficiently process H2 and protons at organometallic FeFe, NiFe, or Fe active sites. Synthetic modeling of the many H2ase states has provided insight into H2ase structure and mechanism, as well as afforded catalysts for the H2 energy vector. Particularly important are hydride-bearing states, with synthetic hydride analogues now known for each hydrogenase class. These hydrides are typically prepared by protonation of low-valent cores. Examples of FeFe and NiFe hydrides derived from H2 have also been prepared. Such chemistry is more developed than mimicry of the redox-inactive monoFe enzyme, although functional models of the latter are now emerging. Advances in physical and theoretical characterization of H2ase enzymes and synthetic models have proven key to the study of hydrides in particular, and will guide modeling efforts toward more robust and active species optimized for practical applications.

Figure 1

Schematic representations of the active sites in [FeFe]-H₂ase (left), [NiFe]-H₂ase (center), and [Fe]-H₂ase (right). The presence of H⁻ and H₂ ligands in [FeFe]-H₂ase and [Fe]-H₂ase, respectively, has yet to be confirmed.

Figure 2

Formation of mono- and dinuclear metal hydrides from low valent metals and H⁺. In the latter case, both bridging and terminal hydrido products are possible.

Figure 3

Interactions of low-valent metal sites with H₂. The η²-H₂ ligand can cleave through oxidative addition to afford dihydride complexes.

Figure 4

Interactions of high-valent metal sites with H₂. The η²-H₂ ligand in high-valent complexes can be acidic and is cleaved through deprotonation (heterolysis).

Figure 5

Fe(η²-H₂) complexes in the laboratory (top left and right) and in Nature (bottom). Note the presence of five strong-field ligands that serve to support the low-spin Fe(II) electrophile.

Figure 6

Thermodynamic parameters for redox and acid–base processes for a metal complex M. Colored arrows denote transfer of an electron (blue), proton (red), H^• (black), and H⁻ (green). Adapted from ref . Copyright 2012 American Chemical Society.

Figure 7

X-ray structure of the [FeFe]-H₂ase active site from Clostridium pasteurianum (PDB code 3C8Y). H atoms are omitted for clarity.

Figure 8

Reconstitution of apo-[FeFe]-H₂ase from Chlamydomonas reinhardtii with [NC(CO)₂Fe(adt)Fe(CO)₂CN]²⁻.^,

Figure 9

Catalytic cycle proposed for [FeFe]-H₂ase (right) and electron counting for the [2Fe] unit in the three characterized states (left). The totals include Fe 3d electrons and bonding electron pairs from donor atoms. The substrate H atoms are in red for emphasis, although they cannot be distinguished from the amine H atoms.

Figure 10

Archetypal diiron thiolato hexacarbonyl [4] can be converted to its hydride [4(μ-H)]⁺ only with very strong acids. An alternative structural representation of [4(μ-H)]⁺, using full arrow and half-arrow notation, is provided below.

Figure 11

Catalytic cycle for electrocatalytic proton reduction mediated by [5(μ-H)].

Figure 12

The 1e⁻ reduction of a diamagnetic Fe(II)(μ-H)Fe(II) hydride affords a Fe(1.5)(μ-H)Fe(1.5) mixed-valent hydride.

Figure 13

Formation and isomerism of the mixed-valent hydride [7(μ-H)]. The μ-H⁻ ligand is unaffected by acid.

Figure 14

Preparation of the dihydride [8(μ-H)(t-H)] from sources of H⁺ and H⁻.

Figure 15

Preparation of a dihydride through oxidative addition.

Figure 16

Preparation (top) and X-ray structures of [11(t-H)]⁺ and ([11(μ-H)]⁺ (bottom). Non-hydride H atoms are omitted for clarity.

Figure 17

Mechanisms for the isomerization of terminal to bridging hydride complexes.

Figure 18

Bridging secondary phosphido ligands do not represent sites for protonation, and only bridging hydrides are observed. In contrast, bridging thiolato ligands can be protonated, and serve as relays to afford terminal and bridging hydride complexes.

Figure 19

Rotated and unrotated isomers of [12], an Fe(I)Fe(I) model for H_red.

Figure 20

Protonation of [15] affords a thiol intermediate en route to a terminal hydride. Formation of the bridging hydride thermodynamic product is acid-catalyzed.

Figure 21

X-ray structures of [16(t-H)]⁺ and [17(t-H)H]²⁺. Nonionizable H atoms are omitted for clarity.^,

Figure 22

Conformational dynamics accompanying the protonation of [17] (inversion of ammonium/amine centers not depicted).

Figure 23

Many proton and electron transfers that can be involved in the HER.

Figure 24

HER mechanism associated with [4].

Figure 25

HER mechanism associated with [18].

Figure 26

HER mechanism associated with [19].

Figure 27

Highly active HER catalyst [17] operates by different mechanisms that depend on acid strength.

Figure 28

HER catalytic cycle proposed for [20], which bears a redox-active phosphole ligand.

Figure 29

H/D scrambling mediated by [6(μ-H)]⁺. This complex may undergo either decarbonylation or μ-H → t-H isomerization such that a vacant site for D₂ binding is accessible.

Figure 30

Stoichometric activation of H₂ with [21]⁺ in the presence and absence of an external oxidant.

Figure 31

Catalytic cycle proposed for [23]-mediated H₂ evolution and oxidation (clockwise and counterclockwise, respectively).^,

Figure 32

Catalytic cycle proposed for H₂ oxidation mediated by PNP complex [24(μ-H)]⁺.

Figure 33

X-ray structure of the [NiFe]-H₂ase active site from Desulfovibrio vulgaris Miyazaki F (PDB code 4U9H). Nonionizable H atoms are omitted for clarity.

Figure 34

Catalytic cycles proposed for [NiFe]-H₂ase. The electronic spin (S) and electron count of the NiFe cores (the sum of 3d electrons and electrons in metal–ligand bonds) are presented below each structure. A H₂O ligand may be weakly bound to Ni in Ni-SI_a.

Figure 35

Alternative mechanism for H₂ activation by [NiFe]-H₂ase, in which a proximal Arg residue (rather than a terminal Cys ligand) relays H⁺ to and from the active site.

Figure 36

Initial work on hydride-containing [NiFe]-H₂ase models focused on the Fe subsite, whose Fe(CO)(CN)₂H fragment is replicated by [25]⁻.

Figure 37

Synthesis of a Ni(I)Fe(I) thiolate [26], which can accept H⁺ either from acid or from H₂ heterolysis to afford the hydride derivative [26(μ-H)]⁺.

Figure 38

X-ray structure of [26(μ-H)]⁺. Non-hydride H atoms are omitted for clarity.

Figure 39

Synthesis of phosphine-substituted Ni(pdt)(μ-H)Fe derivatives is best performed from hydrido tricarbonyl [26(μ-H)]⁺.

Figure 40

Synthesis of NiRu and NiW dithiolates and their respective hydrides.

Figure 41

X-ray structure of [36(μ-H)]⁺, one of the most active synthetic NiFe HER catalysts. Non-hydride H atoms are omitted for clarity.

Figure 42

HER catalytic cycle proposed for the present NiFe dthiolato hydrides.

Figure 43

Interconversion between thiol and hydride tautomers of [43H]⁺. There is evidence for both thiol and hydride moieties in the structure for Ni-R.

Figure 44

DFT-calculated structure for the putative species [44(μ-H)]⁺, whose Ni(III)(μ-H)Fe(II) core mimics that in Ni-C. Non-hydride H atoms omitted for clarity.

Figure 45

NiRu dithiolate [45(OH₂)]²⁺ activates H₂ to afford hydride [45(μ-H)(OH₂)]⁺. Catalytic H₂ oxidation, using Cu²⁺ as the electron acceptor, is proposed to involve a dihydride intermediate.

Figure 46

Activation of H₂ by Ni(II)Fe(II) species [46(MeCN)]²⁺ affords hydride [46(μ-H)]⁺ (top). X-ray structure of [46(μ-H)]⁺ (bottom; non-hydride H atoms omitted for clarity).

Figure 47

Activation of H₂ by in situ generated coordinatively unsaturated Ni(II)Fe(II) species affords hydride models for Ni-R (top). X-ray crystal structure of anion [47(μ-H)]⁻ (bottom; F and non-hydridic H atoms omitted for clarity).

Figure 48

H/D scrambling implies a Ni(η²-H₂) intermediate (top). Such Ni(η²-H₂) species can exhibit heterolysis with and without an external base (middle and bottom, respectively).

Figure 49

Examples of the [Ni(P₂N₂)₂] family of electrocatalysts mediate both H₂ oxidation (counterclockwise) and evolution (clockwise). This cycle is a simplification that neglects certain side pathways, and the order of the steps depends on the identities of substituents R and R′.

Figure 50

X-ray structure of the [Fe]-H₂ase active site from Methanocaldococcus jannaschii (PDB code 3F4Z). H atoms are omitted for clarity.

Figure 51

Catalytic cycle proposed for [Fe]-H₂ase.

Figure 52

Early models for CO-inhibited [Fe]-H₂ase feature some of the donor groups present in the enzyme.^,,

Figure 53

Acyl- and carbamoylpyridine models for CO-inhibited [Fe]-H₂ase.

Figure 54

Pentacoordinate acylpyridine models [59] and [60] replicate inner Fe coordination sphere of the active [Fe]-H₂ase states, yet do not bind H₂.^,

Figure 55

Preparation and reactivity of the Fe hydrido carbamoyl [61(H)H].

Figure 56

Polar hydrogenation of an aldehyde catalyzed by [63]⁺.

Figure 57

Complex [RuCp(CO)₂]⁻ exhibits [Fe]-H₂ase behavior, effecting H₂ heterolysis and delivery of H⁻ to an imidazolium substrate resembling methenyl-H₄MPT⁺.

Figure 58

Proton transport to and from the [2Fe] site in [FeFe]-H₂ase (formal charges omitted). This involves H⁺ movement, denoted by red arrows, between Fe^d, the adt²⁻ cofactor, and the protein (via Cys299), and likely requires pyramidal inversion of the amine.